Human nutritional compositions containing taurine and vitamins and/or minerals

ABSTRACT

Vitamin compositions and/or nutritional mineral compositions containing taurine are provided either alone or in food products, suitable for consumption by human adults.

This is a continuation of application Ser. No. 645,446, filed Aug. 29, 1984, now U.S. Pat. No. 4,629,625.

This invention relates to taurine-containing compositions and the utilization of said compositions for human nutritional purposes. This invention also relates to vitamin and/or mineral-containing compositions useful as nutritional supplements for humans. These compositions can be employed per se as nutritional supplements or incorporated into a comestible, liquid and/or solid, for human consumption.

BACKGROUND OF THE INVENTION

Taurine has been suggested as a component in animal feed, see U.S. Pat. No. 3,636,195. Taurine has also been suggested for incorporation into synthetic infant formulas, see G. E. Gaull U.S. Pat. No. 4,303,692.

Taurine (2-aminoethanesulfonic acid, NH₂ CH₂ CH₂ SO₃ H) is a betasulfonic acid present in high concentrations in animal cells. Taurine and its related compounds, such as hypotaurine (2-aminoethanesulfinic acid) and isethionic acid (2-hydroxyethanesulfonic acid) are formed in animal tissue and vary in concentration from species to species and among tissues. Little, if any, taurine is found in plants.

Additionally, platelets and lymphocytes are found to have present large concentrations of taurine, ranging up to about 50% of the total pool of free amino acids present in these cells. The physiological function of taurine remains unclear, although it is clear that it is an important amino acid for maximal cell viability and homeostasis. Additionally, at least one investigator has termed taurine a "conditionally essential nutrient" meaning that, although the nutrient is not essential for normal subjects, certain individuals, having lost the ability to conserve the compound or having increased requirements due to illness or for other reasons, must supplement their diets with taurine to maintain normal health. Chipponi et al, Am. J. Clin. Nut., 35, (May 1982), pp. 1112-1116; Jacobsen and Smith, Phys. Rev. v. 48, No. 2, (April 1968), pp. 424-511.

The cells of many species possess considerable ability to synthesize taurine, although this is not the case with primates, including man. Certain animals including primates and man have very limited ability to synthesize the amino acid, and rely on diet to maintain taurine stores.

Human B-lymphoblastoid cells take up taurine present in physiological concentrations in plasma, using an active uptake system. These same cells take up taurine when cultured in media supplemented with serum, and show progressive depletion of taurine when cultivated in chemically defined, taurine free media.

Taurine exhibits a positive effect on the number of viable cells in a culture when added to a taurine free medium used in such a culture. Evidence is available which supports the hypothesis that taurine mediates protective action on cell membranes which lead to an increase in cell viability. Huxtable and Bressler, Biochem et Biophys. Acta., 323 (1973), pp. 573-583.

Retinols, the major components of vitamin A, and the related compounds, retinoids, are well known as inhibitors of cell growth. These compounds interact directly with membranes causing increases in permeability and fluidity, and destabilize biological membranes, Stillwell and Bryant, Biochim et Biophys. Acta, 731 (1983) 483-486. This results in hemolysis in erythrocytes, and in increased enzyme secretion in lysosomes. Additionally, when retinols are incorporated into lipid bilayers of liposomes, these are made more permeable to cations and to larger molecules, such as glycine, lysine and glucose. The increase in permeability is often accompanied by decreases in phase temperatures of the liposomes, as well as electrical resistance of the membranes.

Ascorbic acid, i.e. vitamin C, and the related ascorbates, in systems with iron compounds, are known to induce lipid peroxidation of cell membranes, see, e.g. Lewis, Biochem. Pharm. v. 33, No. 11, pp. 1705-14 (1984). The damage that results from this peroxidation is often accompanied by increased membrane permeability, and enhanced water accumulation. When either retinols or iron-ascorbate systems are present, cell viability is decreased due to membrane interference caused by the presence of these, Stillwell and Bryant, op. Cit.; Lewis, op. Cit.

Each of these, i.e. vitamin A (retinol), vitamin C (ascorbic acid or ascorbate), and iron compounds is a necessary nutrient for humans. Hence, removal of these substances from the diet is not possible. In fact, each of these substances may be taken not only through natural occurrence in comestibles, but also through vitamin and mineral nutritional supplements. These supplements are available in a variety of formulations, and often contain well in excess of the amount of each substance necessary for proper nutrition, even when suggested doses are taken. Many who take vitamin supplements, however, believe that increased consumption of these supplements will result in increased beneficial effects. Actually, such increased consumption may lead to increased risk of cell damage, as set forth herein.

Taurine and its physiologically acceptable derivatives have been shown to have a positive effect on cell viability, see, e.g. Alvarez and Storey, Biol. Reprod., 29, 548-555 (1983). Evidence supports the view that taurine mediates a protective effect on cell membranes. Zinc has been shown to exhibit a protective effect on cell membranes as well.

Vitamin E, or tocopherol, is known as having positive effects in counteracting membrane destabilizing actions of retinoids, Stillwell and Bryant, op. Cit.; I. Gery, Inv. Ophthal & Vis. Sci. v. 19 (December 1980) pp. 751-759.

Hence, it is one object of this invention to prepare vitamin compositions having improved nutritional properties.

It is another object of this invention to provide comestibles or food compositions having improved nutritional properties.

How these, as well as other objects of this invention are realized, will be made clear in light of the following disclosure.

SUMMARY OF THE INVENTION

Taurine and its physiologically acceptable derivatives or related compounds are beneficial in maintaining cell homeostasis in humans and animals. Taurine, either alone or together with vitamin E compounds, such as tocopherols, and/or zinc compounds, hinder cell damage caused by vitamin A compounds, such as retinols, and vitamin C compounds, such as ascorbic acid, when the latter is present with iron compounds. Administration of taurine or its physiologically equivalent derivatives or related compounds, either alone or with either vitamin E compounds or zinc compounds, or both, is most readily accomplished by preparing vitamin compositions containing these, together with the vitamin A compounds and/or the vitamin C and iron combination whose affect they inhibit. Such compositions may be prepared in any of the standard ways in which vitamin compositions are prepared, such as pills, capsules and liquids, such as intravenous fluids, or may be incorporated in various comestibles, such as dairy or grain products. Additionally, taurine and its derivatives, along or with vitamin E compounds, or zinc compounds, or with both of these, stabilizes vitamin compositions containing vitamin A, and/or vitamin C and iron compounds.

Vitamin compositions in accordance with this invention comprise or consist essentially of vitamin A and taurine, vitamin C and taurine, vitamin E and taurine and combinations of the above. Nutritional supplements containing taurine are also useful, such as a nutritional supplements containing a physiologically acceptable zinc compound and taurine, a physiologically acceptable iron compound and taurine and combinations thereof alone or with other "minerals", such as a calcium and/or phosphorus compound beneficial for nutrition and health.

DETAILED DESCRIPTION OF THE INVENTION

Various mechanisms and models have been suggested to explain why taurine, alone or with either vitamin E, zinc, or both, stabilizes cell membranes and increases cell viability.

It appears that taurine effectively reverses the inhibition of cell viability caused by excess vitamin A, and iron-ascorbate systems. Additionally, taurine may be combined, either with vitamin E or zinc compounds, to even further reverse inhibition of cell viability caused by vitamin A or iron ascorbate systems.

The usefulness of taurine as an inhibitor of vitamin A and iron-ascorbate related cell damage is best applied in the preparation of vitamin compositions. Many vitamin compositions contain either vitamin A, or iron-ascorbate systems. The following examples support this.

EXAMPLE 1

The contents of the multi-vitamin preparation NATURE'S BOUNTY 1™, is as follows:

    ______________________________________                                         Vitamin or Mineral                                                                             Amount     & U.S. RDA                                          ______________________________________                                         Vitamin A       25,000  IU     500                                             Vitamin D       800     IU     200                                             Vitamin E       30      IU     100                                             Vitamin C       250     mg     417                                             Vitamin B-1     25      mg     1667                                            Vitamin B-2     25      mg     1471                                            Vitamin B-6     50      mg     2500                                            Vitamin B-12    50      mcg    833                                             Niacinamide     50      mg     250                                             Calcium Pantothenate                                                                           50      mg     500                                             Folic Acid      400     mcg    100                                             Biotin          50      mcg     17                                             Choline         15      mg     (none given)                                    Inositol        15      mg     (none given)                                    Paba            50      mg     (none given)                                    Vitamin K       10      mcg    (none given)                                    Iodine          150     mcg    100                                             Iron            10      mg      56                                             Calcium         50      mg      5                                              Phosphorus      23      mg      2                                              Chromium        100     mcg    (none given)                                    Magnesium       100     mg      25                                             Zinc            15      mg     100                                             Manganese       5       mg     (none given)                                    Selenium        25      mcg    (none given)                                    Copper          2       mg     100                                             Potassium       1       mg     (none given)                                    Chloride        1       mg     (none given)                                    Molybdenum      15      mcg    (none given)                                    ______________________________________                                    

EXAMPLE 2

The constituents of VITA-LEA® multimvitamin and multimineral supplements, a product of SHAKLEE Corporation, are as follows:

    ______________________________________                                         Vitamin or Mineral                                                                              Quantity  % U.S. RDA                                          ______________________________________                                         Vitamin A        5000   IU      100%                                           Vitamin D        400    IU     100                                             Vitamin E        30     IU     100                                             Vitamin C        90     mg     150                                             Folic Acid       0.4    mg     100                                             Thiamine         2.1    mg     140                                             Riboflavin       2.4    mg     140                                             Niacin           20     mg     100                                             Vitamin B.sub.6  2      mg     100                                             Vitamin B.sub.12 9      mcg    150                                             Biotin           0.3    mg     100                                             Pantothenic Acid 10     mg     100                                             Calcium          0.6    g       60                                             Phosphorus       0.45   g       45                                             Iodine           150    mcg    100                                             Iron             18     mg     100                                             Magnesium        200    mg      50                                             Copper           2      mg     100                                             Zinc             15     mg     100                                             ______________________________________                                    

EXAMPLE 3

The following are the guidelines of the Expert Panel of the Nutrition Advisory Group, AMA Department of Foods and Nutrition (December 1975), for formulations for intravenously administered vitamins:

    ______________________________________                                                     Infants/Children                                                   Vitamin     (Under 11 years)                                                                            Adult                                                 ______________________________________                                         Vitamin A   2300     IU      3,300 IU (66%)                                    Vitamin D   400      IU      200   IU (50%)                                    Vitamin E   7.0      IU      10.0  IU (33%)                                    Vitamin K   0.2      mg            --                                          Ascorbic Acid                                                                              80.0     mg      100   mg (140%)                                   Folacin     140      mcg     400   mg                                          Niacin      17.0     mg      40.0  mg (200%)                                   Riboflavin  1.4              3.6   mg (210%)                                   Thiamine    1.2              3.0   mg (200%)                                   Vitamin B.sub.6                                                                            1.0      mg      4.0   mg (200%)                                   Vitamin B.sub.12                                                                           1.0      mcg     5.0   mcg (100%)                                  Pantothenic Acid                                                                           5.0      mg      15.0  mg (150%)                                   Biotin      20.0     mcg     60.0  mcg (200%)                                  ______________________________________                                    

(No U.S. RDA percentages are given for children as the recommended amounts vary over the age span given).

EXAMPLE 4

A high potency vitamin supplement prepared by Lederle Laboratories and sold under the registered trademark CENTRUM has the following composition.

    ______________________________________                                         Ingredient     Quantity  % U.S. RDA                                            ______________________________________                                         Vitamin A      5000   I.U.   100                                               Vitamin E      30     I.U.   100                                               Vitamin C      90     mg     150                                               Folic Acid     400    mcg    100                                               Vitamin B.sub.1                                                                               2.25   mg     150                                               Vitamin B.sub.2                                                                               2.6    mg     153                                               Niacinamide    20     mg     100                                               Vitamin B.sub.6                                                                               3      mg     150                                               Vitamin B.sub.12                                                                              9      mcg    150                                               Vitamin D      400    I.U.   100                                               Biotin         45     mcg     15                                               Pantothenic Acid                                                                              10     mg     100                                               Calcium        162    mg      16                                               Phosphorus     125    mg      13                                               Iodine         150    mcg    100                                               Iron           27     mg     150                                               Magnesium      100    mg      25                                               Copper         3      mg     150                                               Manganese      7.5    mg     Not Established                                   Potassium      7.7    mg     Not Established                                   Chloride       7      mg     Not Established                                   Chromium       15     mcg    Not Established                                   Molybdenum     15     mcg    Not Established                                   Selenium       25     mcg    Not Established                                   Zinc           22.5   mg     150                                               ______________________________________                                    

EXAMPLE 5

The prenatal vitamin supplement for use by pregnant and lactating mothers, produced by Lederle Laboratories and sold under the trademark MATERNA, has the following composition.

    ______________________________________                                         Ingredient      Quantity  % U.S. RDA                                           ______________________________________                                         Vitamin A       8000   I.U    100                                              Vitamin D       400    I.U.   100                                              Vitamin E       30     I.U.   100                                              Vitamin C       100    mg     167                                              Folic Acid      1      mg     125                                              Thiamine (Vitamin B.sub.1)                                                                     3      mg     224                                              Riboflavin      3.4    mg     170                                              (Vitamin B.sub.2)                                                              Vitamin B.sub.6 4      mg     160                                              Niacinamide     20     mg     100                                              Vitamin B.sub.12                                                                               12     mcg    150                                              Calcium         250    mg      19                                              Iodine          0.3    mg     200                                              Iron            60     mg     333                                              Magnesium       25     mg      6                                               Copper          2      mg     100                                              Zinc            25     mg     167                                              Docusate Sodium 50     mg     Not Established                                  ______________________________________                                    

In each of Examples 1-5 it is possible to add taurine to these vitamin compositions as an additional or supplemental ingredient. The exceptional large amounts of vitamins A and C in each of these vitamin compositions, taken with the usual practice that many vitamin compositions are taken on a daily basis, indicates that taurine is usefully added to or incorporated in these vitamin compositions to inhibit the effect of any excess these vitamins (vitamins A and C) have on cell viability.

The taurine used in such vitamin compositions may be in the form of the compound itself or any of its salts or other derivative forms which are physiologically acceptable and equivalent. Vitamin E and zinc, along with taurine, also may be added in the form of any of their derivatives which are physiologically acceptable. Formulations containing these substances may vary in the amounts and proportions of the substances therein. For example, in parts by weight or moles, suitable ranges may be:

    ______________________________________                                         Vitamin or Mineral                                                                            Amount (ppw or moles)                                           ______________________________________                                         Vitamin A      0.01-10                                                         Iron           0.01-10                                                         Vitamin C      0.01-30                                                         Taurine        0.01-30                                                         Vitamin E        0-80                                                          Zinc             0-30                                                          ______________________________________                                    

and in percentages by weight:

    ______________________________________                                         Vitamin or Mineral                                                                            pct. by weight or moles                                         ______________________________________                                         Vitamin A      1-20                                                            Iron           1-20                                                            Vitamin C      1-20                                                            Taurine        1-20                                                            Vitamin E      0-20                                                            Zinc           0-20                                                            ______________________________________                                    

The composition of vitamins and minerals as described may be prepared in any of the forms associated with vitamin supplements, such as solids, including but not limited to pills, capsules, and particle forms, and liquids, such as syrups, and preparations suitable for intravenous intake.

The vitamin compositions, as described, may also be incorporated with comestibles and consumed. Many comestibles are enriched by the addition of vitamin supplements thereto, such as enriched breads, ready to eat cereals, and other grain or farinaceous products, as are dairy products, such as breakfast beverages comprising milk and flavored or unflavored milk additives and the like.

Usually, the vitamin and/or mineral compositions of this invention are suitable for self administration, such as in the case of vitamin and/or mineral pills and enriched comestibles. Where, however, the composition is not sutable for self administration, such as in the case of intravenous administration of vitamin supplements, the taurine and either vitamin E or zinc or both may be added separately by the administrator of the supplement or shortly before administration.

As indicated hereinabove, taurine appears to be important for human well being. In accordance with one aspect of this invention, taurine for this purpose is best utilized or administered together with a vitamin, such as vitamin A, vitamin C, vitamin D, vitamin E and/or a B vitamin. Taurine is also usefully administered or taken together with a nutritional supplement, such as a mineral, such as a physiologically acceptable phosphate, calcium compound, chromium compound, magnesium compound, zinc compound, manganese compound, selenium compound, copper compound, potassium compound, a chloride and/or a molybdenum compound. If desired, a composition can also be prepared in accordance with the practices of this invention containing taurine, together with a vitamin, such as those mentioned hereinabove, and a mineral, such as those mentioned hereinabove. These mineral containing compositions may be in liquid or solid (pill, capsule or powder) form or may be included in a food prepared for adult consumption, such as a liquid beverage or solid comestible as a nutritional and/or vitamin supplement therein.

The taurine-containing compositions of this invention, where desirable or necessary, might also include a suitable excipient, which excipient may have a nutritional benefit, as indicated hereinabove, such as a dairy or dairy-like beverage fortified or enriched with compositions of this invention. These taurine-containing compositions, as indicated, may be in liquid form or solid, finely divided form or may be incorporated in conventional well known food materials, e.g. yogurt, drink mixes, spreads, concentrated beverages, peanut butter, margarine, sweetening compositions, synthetic or natural, such as sugar syrups, low calorie synthetic sweetener compositions and the like. As indicated, the practices of this invention may be advantageously utilized in substantially any aspect or use wherein vitamins and/or minerals are incorporated in foods. The important aspect of this invention resides in the utilization of taurine in compositions containing other vitamin and/or nutritional mineral supplements or compositions to provide improved nutrition.

Examples of vitamin compositions and/or nutritional mineral-containing supplements in accordance with this invention are such compositions which contain or consist essentially of about 10-100 milligrams or parts by weight or moles vitamin E and 10-1000 milligrams or parts by weight or moles taurine. When such compositions are expressed in parts by weight or moles, the parts by weight taurine relative to vitamin E in said compositions are based on the total parts by weight or moles taurine and vitamin E in said compositions. Similar such compositions are provided containing or consisting essentially of taurine and vitamin C, taurine and vitamin A, taurine and a B vitamin and taurine and vitamin D and taurine, including compositions containing more than one of the aforesaid vitamins and compositions containing taurine and one or more of the aforesaid minerals and compositions containing taurine and a combination of one or more of the aforesaid vitamins and minerals. 

What is claimed is:
 1. A vitamin composition in liquid form consisting essentially of about 0.1-10 parts by weight or moles of vitamin A, about 0.01-10 parts by weight or moles of an iron compound, about 0.01-10 parts by weight or moles of vitamin C, about 0.01-30 parts by weight or moles of taurine, about 0-80 parts by weight or moles of vitamin E and about 0-30 parts by weight or moles of a zinc compound.
 2. A liquid vitamin composition consisting essentially of about 1-20% by weight or moles of vitamin A, about 1-20% by weight or moles vitamin C, about 1-20% by weight or moles of an iron compound and about 1-20% by weight or moles of taurine.
 3. A liquid vitamin composition in accordance with claim 2 further comprising about 1-20% by weight of vitamin E.
 4. A liquid vitamin composition in accordance with claim 2 further comprising about 1-20% by weight or moles of a zinc compound.
 5. A liquid vitamin composition in accordance with claim 2 further comprising about 0-20% by weight or moles of vitamin E and about 0-20% by weight or moles of a zinc compound. 